Pain sensitisation and joint inflammation in patients with active rheumatoid arthritis.

INTRODUCTION: Despite better therapies and strategies, many people with rheumatoid arthritis (RA) have persistent pain, often from abnormal pain processing, now termed nociplastic pain. However, RA patients with fibromyalgia (FM), a central nociplastic pain syndrome, also have power doppler ultrasound (PDUS+) joint inflammation. To understand the complex causes of pain, we performed clinical examination and patient-reported outcome measures (PROMs) plus comprehensive PDUS evaluation not previously combined. METHODS: In a cross-sectional study of sequential RA patients with at least moderate DAS28 erythrocyte sedimentation rate disease activity, we assessed 66/68 joints for swelling and tenderness, respectively, FM American College of Rheumatology 2010 diagnostic criteria, completed PROMs for function, quality of life and mood, alongside PDUS examination of 44 joints. Statistical analysis included logistic regression modelling and regularised (lasso) logistic regression methods. RESULTS: From 158 patients, 72 (46%) patients met FM criteria, with significantly worse tender joint counts and PROMs, but no differences in PDUS compared with the non-FM group. Categorising patients by PDUS+ joint presence and/or FM criteria, we identified four distinct groups: 43 (27.2%) patients with -FM-PD, 43 (27.2%) with -FM+PD, 42 (26.6%) with +FM-PD and 30 (19%) with +FM+PD. Both FM+ groups had worse PROMs for fatigue, mood and pain, compared with the FM- groups. We were unable to develop algorithms to identify different groups. CONCLUSION: The unexpected group -FM-PD group may have peripheral nociplastic pain, not commonly recognised in rheumatology. Only 46% of patients demonstrated PDUS+ inflammation. However clinical examination and PROMs did not reliably differentiate groups, emphasising PDUS remains an important tool.

Polyfunctional, Proinflammatory, Tissue-Resident Memory Phenotype and Function of Synovial Interleukin-17A+CD8+ T Cells in Psoriatic Arthritis.

OBJECTIVE: Genetic associations imply a role for CD8+ T cells and the interleukin-23 (IL-23)/IL-17 axis in psoriatic arthritis (PsA) and other spondyloarthritides (SpA). IL-17A+CD8+ (Tc17) T cells are enriched in the synovial fluid (SF) of patients with PsA, and IL-17A blockade is clinically efficacious in PsA/SpA. This study was undertaken to determine the immunophenotype, molecular profile, and function of synovial Tc17 cells in order to elucidate their role in PsA/SpA pathogenesis. METHODS: Peripheral blood (PB) and SF mononuclear cells were isolated from patients with PsA or other types of SpA. Cells were phenotypically, transcriptionally, and functionally analyzed by flow cytometry (n = 6-18), T cell receptor ß (TCRß) sequencing (n = 3), RNA-Seq (n = 3), quantitative reverse transcriptase-polymerase chain reaction (n = 4), and Luminex or enzyme-linked immunosorbent assay (n = 4-16). RESULTS: IL-17A+CD8+ T cells were predominantly TCRαß+ and their frequencies were increased in the SF versus the PB of patients with established PsA (P < 0.0001) or other SpA (P = 0.0009). TCRß sequencing showed that these cells were polyclonal in PsA (median clonality 0.08), while RNA-Seq and deep immunophenotyping revealed that PsA synovial Tc17 cells had hallmarks of Th17 cells (RORC/IL23R/CCR6/CD161) and Tc1 cells (granzyme A/B). Synovial Tc17 cells showed a strong tissue-resident memory T (Trm) cell signature and secreted a range of proinflammatory cytokines. We identified CXCR6 as a marker for synovial Tc17 cells, and increased levels of CXCR6 ligand CXCL16 in PsA SF (P = 0.0005), which may contribute to their retention in the joint. CONCLUSION: Our results identify synovial Tc17 cells as a polyclonal subset of Trm cells characterized by polyfunctional, proinflammatory mediator production and CXCR6 expression. The molecular signature and functional profiling of these cells may help explain how Tc17 cells can contribute to synovial inflammation and disease persistence in PsA and possibly other types of SpA.

Pulmonary artery aneurysms in Behçet's disease treated with anti-TNFα: A case series and review of the literature.

Behçet's disease (BD) is a systemic inflammatory disorder of unknown aetiology. Pulmonary haemorrhage from ruptured pulmonary artery aneurysms (PAA) in this condition carries a high mortality but treatment has largely been empiric with use of glucocorticoids and cyclophosphamide. Tumour necrosis factor α (TNF-α) was recently recognised as a mediator in the pathogenesis of BD inflammatory lesions. TNFα inhibitors have been shown in various case reports/series to have beneficial effects in uveoretinitis, entero-Behçet's, neuro-Behçet's and BD arthritis. We describe the efficacy and tolerability of infliximab in 2 patients with Behçet's disease complicated by pulmonary vasculitis admitted to our unit during the years 2004-2015, and discuss the previously published data in this area.

Complementary and alternative medicine use in patients with gout: a longitudinal observational study.

BACKGROUND: Complementary and alternative medicine (CAM) is frequently used by patients with arthritis. OBJECTIVES: The objectives of this study were to determine the frequency and type of CAM used for gout, to understand the clinical and psychological factors associated with CAM use in people with gout, and to determine whether patients using CAM have different clinical outcomes over 1 year. METHODS: A total of 276 patients with gout for less than 10 years' duration were recruited into a longitudinal observational study. Complementary and alternative medicine information including frequency, type, and cost of therapies were recorded at baseline. Gout disease activity (including flare frequency, tophus count, Health Assessment Questionnaire II, and serum urate) was assessed at baseline and after 1 year. RESULTS: Complementary and alternative medicine use was reported by 23.9% of patients. A diverse range of CAM was used, most commonly dietary supplements and vitamins. Patients using CAM reported higher levels of concern about their gout but did not differ from those not taking CAM with respect to age, sex, years of formal education, ethnicity, illness perceptions, or gout disease activity measures at baseline or after 1 year. Total costs at baseline related to gout therapy were higher in the CAM users compared with those not using CAM (mean [SD] cost per month NZ $35.7 [NZ $69.0] vs NZ $7.1 [NZ $22.8]; P = 0.001). CONCLUSIONS: Complementary and alternative medicine use is not uncommon in patients with gout, albeit less than is reported in other rheumatic diseases. Inquiry about CAM use should be incorporated into the clinical assessment of patients with gout, to develop treatment plans that best suit the individual patient's health beliefs.

Insights into rheumatoid arthritis from use of MRI.

Magnetic resonance imaging (MRI) is ideal for imaging the joints of rheumatoid arthritis (RA) patients. It produces anatomically detailed images of bone, cartilage, tendons and synovial membrane. It can reveal structural damage, in the form of bone erosion, cartilage thinning and/or tendon rupture, and regions of inflammation, using sequences that reveal water content and vascularity. MRI synovitis, tenosynovitis and bone oedema/osteitis all have prognostic significance, and MRI studies of RA have helped elucidate the mechanisms whereby bone and synovial inflammation lead to joint damage. Bone oedema/osteitis has become an important imaging biomarker, and can be used to help predict progression from undifferentiated arthritis to definite RA. Recent MRI studies have confirmed that subclinical inflammation is often present in patients in clinical remission, and these data may affect disease management. Finally, recent clinical trials are reviewed, in which MRI outcome measures are being established as sensitive response markers.

Valproate-induced hyperammonaemia superimposed upon severe neuropsychiatric lupus: a case report and review of the literature.

This paper presents a case of systemic lupus erythematosus (SLE) with neuropsychiatric features, where the outcome was influenced by the development of hyperammonaemia, probably induced by sodium valproate. A case of severe SLE occurring in a 20-year-old Maori girl is described. Her disease had been characterised by neuropsychiatric features for several years, culminating in persistent seizure activity at the time of her final presentation. Her management with anticonvulsants was complicated by the development of intractable hyperammonaemia which contributed to irreversible clinical deterioration. We have reviewed the English literature for reports of valproate-related hyperammonaemia which has often been described in the setting of seizure and mood disorders. This is the first case where it has been reported, superimposed upon severe neuropsychiatric SLE (NP-SLE). The mechanism by which valproate induces hyperammonaemia remains incompletely understood but is likely to relate to the urea cycle. Under normal metabolic conditions, acyl-CoA is transported into the mitochondria via a carnitine transport system. It is then converted to acetyl-CoA via ß-oxidation and eventually to N-acetyl glutamate. This pathway can be interrupted by the introduction of sodium valproate, leading to a reduction of free coenzyme A, acetyl-CoA and carnitine, and resulting in the decreased availability of cofactors necessary for the function of the urea cycle. As this is the primary means of ammonia metabolism, serious elevation in serum ammonia levels may occur in patients on this anticonvulsant medication. In this patient with active NP-SLE, the combined autoimmune and metabolic brain insult contributed to a fatal outcome.